research article open access favourable ten-year overall

RESEARCH ARTICLE Open Access

Favourable ten-year overall survival in aCaucasian population with high probability ofhereditary breast cancerLaura Cortesi1*, Cristina Masini1, Claudia Cirilli2, Veronica Medici1, Isabella Marchi1, Giovanna Cavazzini3,Giuseppe Pasini4, Daniela Turchetti5, Massimo Federico1

Abstract

Background: The purpose of our study was to compare differences in the prognosis of breast cancer (BC) patientsat high (H) risk or intermediate slightly (IS) increased risk based on family history and those without a family historyof BC, and to evaluate whether ten-year overall survival can be considered a good indicator of BRCA1 genemutation.

Methods: We classified 5923 breast cancer patients registered between 1988 and 2006 at the Department ofOncology and Haematology in Modena, Italy, into one of three different risk categories according to Modenacriteria. One thousand eleven patients at H and IS increased risk were tested for BRCA1/2 mutations. The overallsurvival (OS) and disease free survival (DFS) were the study end-points.

Results: Eighty BRCA1 carriers were identified. A statistically significantly better prognosis was observed for patientsbelonging to the H risk category with respect to women in the IS and sporadic groups (82% vs.75% vs.73%,respectively; p < 0.0001). Comparing only BRCA1 carriers with BRCA-negative and sporadic BC (77% vs.77% vs.73%,respectively; p < 0.001) an advantage in OS was seen.

Conclusions: Patients belonging to a population with a high probability of being BRCA1 carriers had a betterprognosis than those with sporadic BC. Considering these results, women who previously had BC and had survivedten years could be selected for BRCA1 analysis among family members at high risk of hereditary BC during geneticcounselling. Since only 30% of patients with a high probability of having hereditary BC have BRCA1 mutations,selecting women with a long term survival among this population could increase the rate of positive analyses,avoiding the use of expensive tests.

BackgroundThe major breast cancer (BC) predisposing genes,BRCA1 and BRCA2 were identified in 1994 and 1995,respectively [1,2]. Unfortunately, the optimal clinicalapproach to women who develop hereditary breast can-cer remains incompletely defined. Studies of the out-comes of women with BRCA1/BRCA2-related cancerhave yielded conflicting results. Several reports sug-gested that women with germline mutations in BRCA1are more likely to die from their disease than arewomen with sporadic breast cancer [3-6], whereas

BRCA2 mutation carriers and non-mutation carriersseem to share a similar prognosis [7,8]. The poor prog-nosis in BRCA1 carriers may be consistent with thehistological characteristics usually described for BRCA1-associated breast cancer, which show higher histologicgrade and cancers that are more often hormone recep-tor-negative than sporadic breast cancer cases [9-12].However, Bonadona et al. found no evidence for poorershort-term survival in BRCA1 mutation carriers com-pared with non-carriers in a prospective population-based cohort [13]. Apart from a simple interest in theepidemiological aspects of breast malignancy, knowledgeof the associated mortality is important to the familiesof patients with BC and to clinicians and scientists

* Correspondence: [email protected] of Oncology and Haematology, University of Modena andReggio Emilia, Modena, Italy

Cortesi et al. BMC Cancer 2010, 10:90http://www.biomedcentral.com/1471-2407/10/90

© 2010 Cortesi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

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involved in trying to improve the outcomes of breastcancer. The results of a recent study in an AshkenaziJewish population suggested that among the subgroupof patients with BC carrying a BRCA1 mutation, thosewho received chemotherapy had a better survival ratecompared with those who did not [8].The primary aim of our study was to calculate disease

free survival (DFS) and overall survival (OS) of BCpatients at high risk (H) or intermediate slightly (IS)increased risk based on family history and those withouta family history of breast cancer using the populationregistered with the Breast Cancer Registry in Modena.Previous studies were aimed at evaluating the outcomein BRCA-positive and BRCA-negativepatients, but noneshowed a significant survival difference between differ-ent risk categories. In case of statistically significant dif-ferences in OS between the three groups, a secondaryaim was to determine whether patients with a betterprognosis were BRCA1 mutation carriers, showing thatthe outcome could be considered an indicator of BRCA1inheritance. Additionally, we evaluated whether che-motherapy could play a role in the prognosis of BRCA1carriers, providing more benefit in this patient popula-tion than in patients with sporadic breast cancer.

MethodsPatientsPatients included in our analysis were diagnosedbetween 1988 and 2006 at the Department of Oncologyand Haematology in Modena. All newly-diagnosed,biopsy-proven primary breast cancer patients were eval-uated. The family history was collected and classifiedaccording to the Modena criteria (without family his-tory, IS increased risk, or H risk)[14] and a blood sam-ple, preserved with EDTA, was obtained with informedconsent and frozen at -80°C for biological studies. Onthe basis of the Modena criteria for familial risk,patients who did not have any family history were con-sidered to have sporadic breast cancer, patients with oneor two breast cancers at ≥ 40 years, without a first-degree relationship, were considered at IS increased risk,and patients with breast cancer at ≤ 35 years, three ormore breast cancers with a first-degree relationship, andat least one case at ≤ 40 years or bilateral breast cancerhad a H risk of being hereditary.All research regarding the identification, counselling,

genetic testing, and clinical data regarding individuals atrisk of developing breast cancer were ethically approvedby the Ethics Commitee of Modena (reference number45/00).

Mutational analysisIn 1995, DNA started to be extracted from frozen wholeblood using the Invisorb Blood Universal kit (Invitek,

Berlin, Germany), amplified by PCR using primers speci-fic for the coding sequence and exon-intron boundariesof BRCA1, and analyzed by Direct Automated Sequen-cing using an ABI Prism 3100 (Applied Biosystems, Fos-ter City, CA). Subsequently, patients with breast cancerprovided consent for genetic testing that was completedfor each case.Samples negative for BRCA1 mutations were tested for

BRCA1 rearrangements using the multiplex ligation-dependent probe amplification assay (MRC Holland,Amsterdam, The Netherlands) following the manufac-turer’s protocol.

Statistical analysisThe c2 test was used to determine differences in clinico-pathological features between groups. Survival curveswere estimated using the Kaplan-Meier method includ-ing the log-rank test group comparison. Patients whowere BRCA1 carriers were matched with patients withsporadic breast cancer from the Modena cancer registry.This registry, initiated in 1988, covers an area withapproximately 650,000 inhabitants in Northern Italy. Adatabase with a total of 3858 cases of sporadic breastcancer was used to find four matched controls for eachcase and a randomized matches were assigned betweenBRCA1 and patients with sporadic BC of the same ageat diagnosis (range, between 26 and 76 ± 4 years),tumour grade (I, II, and III), and stage (I, II, and III).Multivariate analyses of DFS and OS were conductedusing a proportional hazards Cox regression model. Allstatistical analyses were done with SPSS, version 12.0(SPSS Inc, Chicago, IL).

ResultsPatient CharacteristicsFrom January 1988 and December 2006, 5923 patientswere diagnosed with breast cancer. According to theirfamily history, 4912 were considered sporadic breastcancers, 691 were at IS increased risk, and 320 wereconsidered H risk. The patients’ characteristics aredetailed in Table 1. The H risk group presented with amedullary carcinoma histotype more frequently than theother two groups (p < .0001). The H risk group wasmore likely to have stage II disease than the sporadicand IS increased risk groups (p < .0001), and to have asignificantly lower estrogen receptor (ER) and progester-one receptor (PgR) expression levels (p < .0001) as mea-sured by immunohistochemical analysis (clone 6F11,Ventana, for ER; and clone 1E2, Ventana, for PgR) andstained by Ventana Benchmark autostainer. The ER andPgR receptor status was tested by evaluating the percen-tage of nuclear immunoreactivity with respect to all thenuclei in the neoplastic cells, independently of the stain-ing intensity. No differences were seen in the Ki67 level


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between the groups (p = .17). The proportion of patientswho received adjuvant chemotherapy was greater in theIS increased risk group than in the other two groups(p < .0001). The most frequent chemotherapy strategywas anthracycline-based followed by taxanes and theCMF regimen. The most frequently used first line che-motherapy regimen was platinum based, followed by aCMF scheme. The proportion of patients who receivedadjuvant hormone therapy was lower in the H risk groupthan in the other two groups, according to the negativehormonal receptor status (p < .0001).

Mutational AnalysisThe BRCA1 mutational analysis was only performed inpatients belonging to the H and IS risk groups, with a

22.8% (73/320) and 1.0% (7/691) mutation rate, respec-tively. In total, 80 patients were BRCA1 carriers.

Survival analysisOverall, 5923 patients were followed until December2006, resulting in a median follow-up time of 72months. In all, 1302 deaths (1074 sporadic, 174 ISincreased risk, and 54 H risk) and 1137 relapses (884sporadic, 186 IS increased risk, and 67 H risk) werereported. The estimated 10-year overall survival rate was82% for the H risk patients, 75% for the IS increasedrisk group, and 73% for patients with sporadic breastcancer (log-rank p < .0001; Fig. 1A). The estimated 10-year DFS was 72% in the H risk group, 70% in the ISincreased risk group, and 75% in patients with sporadic

Table 1 Clinicopathological characteristics of patients according to familial risk group

Family Risk Group

No family history Intermediate-Slightly increased risk High Risk p

(n = 4912) (n = 691) (n = 320)

Characterics N° % N° % N° %

Histotype

Ductal 3936 80.1 565 81.8 251 78.4 NS

Lobular 606 12.3 83 12.0 44 13.7 NS

Tubular 93 1.9 13 1.9 2 0.6 NS

Colloid 64 1.3 10 1.4 0 0 NS

Medullary 26 0.5 6 0.9 13 4.1 < .0001

Other 187 3.9 14 2.0 10 3.2 NS

Stage

I 2322 47.3 312 45.1 141 44.1 NS

II 1546 31.5 255 36.9 127 39.7 < .0001

III 802 16.4 112 16.2 48 15.0 NS

IV 216 4.4 11 1.8 1 0.3 <.0001

X 23 0.5 1 0.1 3 0.9 NS

ER

Positive 3286 66.8 448 64.8 147 45.9 < .0001

Negative 757 15.4 139 20.2 149 46.6 < .0001

Unknown 869 17.8 103 15.0 24 7.5 < .0001

PgR

Positive 2796 56.9 408 59.1 135 42.2 < .0001

Negative 1109 22.5 173 25.0 162 50.6 < .0001

Unknown 1007 20.6 110 15.9 23 7.2 < .0001

Ki67

Low (0-19) 2523 51.4 383 55.4 185 57.8 NS

High (20-100) 1109 22.5 167 24.2 103 32.2 NS

Unknown 1007 20.6 141 20.4 32 10.0 NS

Chemotherapy

Yes 1851 37.7 350 50.7 106 33.1 < .0001

No 3061 62.3 341 49.3 214 66.9 < .0001

Hormone therapy

Yes 2804 57.1 380 55.0 106 33.1 < .0001

No 2108 42.9 311 45.0 214 66.9 < .0001

Abbreviations: ER, estrogen receptor; PgR, progesterone receptor


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Figure 1 Overall survival and disease free survival according to risk group (A, C) and to BRCA1 status (B, D).


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breast cancer (log-rank p = .12; Fig. 1C). After thegenetic analysis, 80 patients were classified as BRCA1carriers and 931 were considered BRCA negative. In theBRCA1 carrier group, 8 deaths (5 caused by a secondtumour arising after breast cancer) and 13 relapses (6local recurrences and 7 distant recurrences) werereported, whereas in the BRCA negative group 220deaths and 240 relapses occurred. The 10-year overallsurvival rate was 77% for BRCA1 carriers, 77% forBRCA-negative patients, and 73% for sporadic breastcancer (log-rank p < .001; Fig. 1B). The 10-year DFSwas 75% in sporadic breast cancer, 70% in the BRCA-negative patients, and 70% in the BRCA1 group (log-rank p = .45; Fig. 1D).The study group of 80 BRCA1 cases was compared

with 320 matched sporadic cases from the Modena can-cer registry which were the same age, and had the sametumour grade and stage. Results are shown in Fig. 2. Astatistically significant difference in OS was seen forBRCA1 patients compared with sporadic BC (85% vs.73%, respectively, p = .05).According to the hormone receptor status, the hor-

mone receptor-negative patients in the H risk groupand the BRCA1 patients had a better OS (Fig. 3A, B)while a hormone receptor-positive advantage was onlyseen in the H risk group, but not in the BRCA1 group(Fig. 3C, D).

Multivariate survival analysis according to prognosticfactors and chemotherapyOf the 5923 patients, 5012 were included in multivariateanalyses, which included BRCA1 status, disease stage,ER status, PgR status, grading, age, and chemotherapy.The BRCA1 positive and negative status was a signifi-cant independent factor for improved OS (HR = 0.29;p = .002 and HR = 0.76; p = < .001, respectively) com-pared with the sporadic breast cancer cases. Positive ERand PgR status was associated with a better OS (HR =0.82; p = .03 and HR = 0.79; p = .004, respectively).Also, chemotherapy was an important factor in reducingthe mortality rate (HR = 0.68; p < .0001). Stage > I(HR = 3.49; p < .0001) and grading III (HR = 1.39; p <.0001) were significant factors for poorer OS. Youngerage (≤ 35 years) represented a risk factor for a shorterOS, but the trend was not statistically significant. In amodel that included 2213 patients receiving chemother-apy, BRCA1-positive status (HR = 0.38; p = .05) but notBRCA1-negative status (HR = 0.97; p = .79) reduced themortality rate. Positive PgR status (HR = 0.76; p = .021)was a favourable factor as was positive ER status (HR =0.76; p = .083), but did not reach statistical significance.Stage > I (HR = 3.55; p < .0001) and grading III (HR =1.38; p < .0001) were factors statistically associated withan increased risk of death. There was a similar but nonsignificant trend in age ≤ 35 years (HR = 1.15; p = .44).Conversely, in a model without chemotherapy, theBRCA1-positive status lost statistical significance inreducing mortality (HR = 0.23; p = 0.056), whereas theBRCA1-negative status maintained its favourable impact(HR = 0.56; p < .0001). Also, positive ER (HR = 0.82,p = .17) and PgR status (HR = 0.82; p = .08) and ageless than 35 years (HR = 0.95;p = .85) did not affect OS.Finally, stage > 1 (HR = 3.43; p < .0001) and grading III(HR = 1.39; p < .0001) were statistically associated withan increased risk of death. Detailed results for multivari-ate analysis are shown in Table 2.In comparing BRCA1 patients who did or did not

receive chemotherapy, no difference was seen in termsof OS (see Fig. 4), even if all the death events in thetreated group of patients were derived from secondtumours (4 cases).

DiscussionThe results of this large analysis show that patients con-sidered at H risk of being BRCA1 carriers had a betterOS than patients considered at IS increased risk or tohave sporadic breast cancer. This difference was alsomaintained in BRCA1 carriers with respect to BRCA1-negative and sporadic breast cancer patients. Notably,91.2% (73/80) of BRCA1 carriers were identified in theH risk group, and may explain the survival advantage inthis group of patients, even if other reasons may be

Figure 2 Probability of survival in 80 BRCA1 breast cancercases and 320 sporadic breast cancer controls matched for ageand tumour grade and stage, using Kaplan-Meier analysis.There was a statistically significant difference between the twogroups (log-rank test, p = .05).


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Figure 3 Overall survival according to risk group in hormone receptor negative (A) and positive (C) patient subgroups, and accordingto BRCA1 status in hormone receptor negative (B) and positive (D) patient subgroups.


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involved. Patients who know they are at high risk ofdeveloping breast cancer may be more likely to partici-pate in surveillance programs and start at a youngerage, receive an earlier diagnosis, and subsequently,experience a better outcome.One of the most important findings of our study was

that the survival difference was attributable, in a multi-variate analysis, to the patient’s BRCA1 status and wasobserved in patients treated with chemotherapy. Thisfinding is important when, as happens in a family cancercentre like in ours, we are faced with a patient or ahealthy woman who has a family history of breast

cancer. By collecting all the information about indivi-duals affected by breast cancer, very long-term survivorscan be identified by predicting a predisposition for beinga BRCA1-mutation carrier in the descendants. Further-more, BRCA1 carriers may be more likely to be foundamong women who have a high probability of hereditarybreast cancer and who have a long term survival. IfBRCA1 carriers could be identified through these char-acteristics, the use of expensive tests could be avoidedand the rate of positive analyses increased.Our study involves a very large number of Caucasian

patients with breast cancer (N = 5923) who were firstevaluated for their family history of breast cancer andsubsequently for BRCA1 status. The most commonweakness of previous studies includes the small numberof patients or selection bias, such as a retrospective ana-lysis for BRCA1 status. Owing to the large number ofsubjects, we could calculate OS differences between riskgroups, and even in subgroup analyses.Unexpectedly, the survival difference according to H

risk and BRCA1 status was not related to the DFS. Thisfinding shows that the H risk and BRCA1 patients havethe same DFS as the other two groups, but seem torespond better to chemotherapeutic agents. This findingis in contrast with the results of Rennert et al. [8] whoshowed an insignificant difference in OS between BRCAcarriers and non carriers and between BRCA1 carriersand BRCA-negative patients treated with chemotherapy.Our argument is that, in BRCA1 patients, 41% ofrelapses were local recurrences, whereas in patients withsporadic BC the local recurrence rate was 25%, and dis-tant metastases accounted for 75%. Consequently, it is

Table 2 Cox’s proportional hazard regression models foroverall survival

Variable N° (%) HR p [95% CI]

All cases 5012 (85)

Sporadic 4172 (83) 1.00 - -

BRCA - 785 (16) 0.76 < .001 0.64 to 0.89

BRCA1+ 55 (1) 0.29 .002 0.13 to 0.62

stage > 1 2372 (47) 3.49 < .0001 3.01 to 4.04

Estrogen receptorpositive

4090 (82) 0.82 .03 0.69 to 0.98

Progesterone receptorpositive

3138 (64) 0.79 .004 0.67 to 0.93

Chemotherapy, yes 2213 (44) 0.68 < .0001 0.59 to 0.77

Age ≤ 35 199 (4) 1.12 .42 0.84 to 1.49

Grading III 1778 (35) 1.39 < .0001 1.22 to 1.58

Model with chemotherapy 2213 (44)

Sporadic 1780 (36) 1.00 - -

BRCA- 404 (8) 0.97 0.79 0.78 to 1.20

BRCA1+ 29 (2) 0.38 .05 0.14 to 0.99

Stage > I 1689 (76) 3.55 < .0001 2.65 to 4.76


1571 (71) 0.81 .083 0.65 to 1.02


1492 (67) 0.76 .021 0.61 to 0.96

Age ≤ 35 years 128 (6) 1.15 .44 0.81 to 1.62

Grading III 1116 (50) 1.38 < .0001 1.15 to 1.64

Model withoutchemotherapy

2799 (56)

Sporadic 2392 (85) 1.00 - -

BRCA- 381 (14) 0.56 < .0001 0.43 to 0.73

BRCA1+ 26 (1) 0.23 .056 0.14 to 1.02

stage > I 951 (34) 3.43 < .0001 2.89 to 4.09


2519 (90) 0.82 .17 0.63 to 1.08


2298 (82) 0.82 .08 0.65 to 1.03

Age ≤ 35 71 (3) 0.95 .85 0.56 to 1.60

Grading III 662 (24) 1.39 < .0001 1.15 to 1.68

Abbreviations: HR, hazard ratio; CI, confidence interval

Figure 4 A comparison of the group of BRCA1 patients whoreceived or did not receive chemotherapy did not show anydifference in overall survival (log-rank test, p = .69).


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not surprising that a difference in OS was found andcould be explained by the use of alkylating agents, suchas platinum-derived drugs, in metastatic disease that arewell known to be more effective in BRCA-relatedtumours [15]. Furthermore, since BRCA1 patients main-tain a statistically significant OS advantage, even aftermatching each case to four controls for age and tumourgrade and disease stage, this result is very important interms of its practical value, because all confoundershave been removed.Robson et al [12] suggested that a BRCA1 mutation

was an independent predictor of breast cancer mortalityin a multivariate analysis of a group of women who didnot receive chemotherapy, but not in women whoreceived adjuvant chemotherapy.In a multivariate analysis, we found that chemotherapy

is a prognostic factor for better survival in all patientscombined; furthermore, we found that a BRCA1-positivestatus was an independent predictor for a better survivalin all patients and also in the subgroup of patients whoreceived chemotherapy, but not in patients who did notreceive chemotherapy. No differences are shown forBRCA1 patients, independently of chemotherapy or not.Also, this result might be explained by the fact thatdeaths in the treated group of patients were all relatedto a second tumour, while in the non treated group oneof three deaths was caused by breast cancer. In conclu-sion, chemotherapy has a greater protective effect inBRCA1 mutation carriers compared with patients whoare BRCA-negative and those with sporadic breast can-cer. Furthermore, since BRCA1-related tumours aremore likely to be triple negative, the greatest advantagewas shown for ER-negative breast cancer, were che-motherapy is the most active. Hence, increasing thenumber of BRCA1 carriers identified by correctly select-ing patients with a high probability of having hereditarybreast cancer through a 10-year survival analysis couldimprove the benefit derived from specific chemotherapyagents (i.e., alkylating or PARP-inhibitors).In fact, the chemotherapy benefit is well known

because normal BRCA1 and BRCA2 proteins participatewith RAD51 in the repair of double-stranded DNAbreaks induced by DNA-damaging agents [16-19]. Thebetter prognosis could be due to the deficiency of theBRCA proteins, which confer substantial cellular sensi-tivity to the inhibition of poly (ADP-Ribose) polymeraseenzyme (PARP). This polymerase is a key enzyme in therepair of single-stranded DNA damage via the base exci-sion repair pathway. The loss of PARP activity in BRCAmutant cells might lead to the persistence of DNAlesions normally repaired by homologous recombination,resulting in increased chromosome instability and pro-grammed cell death specifically in tumour cells [20,21].Therefore, because there is no functional protein within

the tumour cells, they lose their capacity to repair DNAdamage. This might be specifically pronounced fordrugs, such as cisplatin, acting through the induction ofDNA damage leading to cell death and to a better thera-peutic response. In a small clinical study, Chappuis et al[22] found a benefit in Ashkenazi Jews with locallyadvanced breast cancer who were BRCA-positive andtreated with anthracycline-based chemotherapy regi-mens. In this study, all patients received anthracycline-based neoadjuvant chemotherapy, and 10 of 11 patientswith BRCA mutations had a clinical complete responsecompared with only 8 of 27 BRCA-negative patientswith sporadic breast tumours. From this study, it wasinferred that tumours with BRCA1 mutations are highlysensitive to anthracycline-based chemotherapy regimens.In our study, patients were considered part of a hospi-

tal-based population and were not selected for age,tumour stage, or treatment, which could influence survi-val rates. We were successful in obtaining blood samplesfrom all patients and were able to genotype all the sam-ples we received. The patients were followed for a med-ian of 72 months. Treatment regimens were chosen onthe basis of disease staging. The Modena Cancer Registrycaptures outcome data from almost all patients with can-cer who are treated in the province. Data on pathologicaldiagnosis are verified by a pathologist, and incompleteinformation is retrieved from medical records when pos-sible. All patients were Caucasian, and it is possible thatthe chemotherapy sensitivity can be associated with spe-cific modifier genes not found in other populations.Our study has a number of limitations. Tumour stage

and hormone receptor status were not routinelyrecorded, particularly during the first period. Since wetested only a subpopulation of patients with a positivefamily history of breast cancer, it is possible that somehereditary cases were misclassified; but we found thatonly 1% of mutations occurred in the IS increased riskgroup suggesting that the number of BRCA1 carriers inthe sporadic group would be very low. Since we identi-fied only 80 mutation carriers, the subgroup analysisrelied on a small number of subjects.In conclusion, our study is the first to evaluate a rela-

tionship between familial risk of breast cancer and agenetic assessment in terms of DFS and OS. We pro-pose that the increased survival associated with a familyhistory of breast cancer, suggesting hereditary breastcancer according to the Modena criteria, should be con-sidered with respect to BRCA1 analysis as a predictor ofmutations. We feel that randomized studies need to bedesigned to further address the relationship betweenBRCA1 mutations and sensitivity to chemotherapy, andfurther clinical investigations are required to determinewhether the BRCA1 status can be used to predict treat-ment outcomes.


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ConclusionsIn conclusion, our data show that patients belonging toa population with a high probability of being BRCA1carriers have a better prognosis than other risk groups,and this could be considered an indicator of BRCA1inheritance. This paper provides, for the first time, evi-dence-based proof that women at high risk of beingBRCA1 carriers have a favorable prognosis after 10 yearsfollow-up.

AcknowledgementsAssociazione Angela Serra per la Ricerca sul Cancro; Euro MediterraneanNetwork for Genetic Services-Coordination Action (Grant to the Budget) -Contract n° INCO-CT-2006-031968

Author details1Department of Oncology and Haematology, University of Modena andReggio Emilia, Modena, Italy. 2Modena Cancer Registry, Modena, Italy.3Department of Oncology and Haematology, Carlo Poma Hospital, Mantua,Italy. 4Department of Medical Oncology and Oncohaematology, CityHospital, Rimini, Italy. 5Medical Genetic Service, University of Bologna,Bologna, Italy.

Authors’ contributionsLC participated in the design of the study and drafted the manuscript. CMacquired the data and performed the statistical analysis. CC participated inthe statistical analysis. VM performed the genetic testing. IM acquired thedata from the centre. GC participated in the collection of patient data fromMantua Hospital. GP participated in the collection of patient data fromRimini Hospital.DT participated in the collection of patient data from Bologna Hospital. MFdesigned the study and revised the final manuscript. All authors read andapproved the final manuscript.

Competing interestsThe authors declare that they have no competing interests.

Received: 7 April 2009 Accepted: 10 March 2010Published: 10 March 2010

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Pre-publication historyThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/10/90/prepub

doi:10.1186/1471-2407-10-90Cite this article as: Cortesi et al.: Favourable ten-year overall survival ina Caucasian population with high probability of hereditary breastcancer. BMC Cancer 2010 10:90.


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